Gastro-Adeno-Papilloma Flashcards
Viral Gastroenteritis
inflamm of?
important diseased of?
leading cause of?
– Inflammation of stomach or intestines
– important disease of infants and children
– leading cause of childhood death in developing countries
viral cause of gastroeneritis
rotavirus and group A, b and c genomes
segemented dsRNA
medical significance of group A reovirdiae
major cause of diarrhea in infants
norovirus significance
major cause of diarrhea outbreaks in adults/children
~____% of diarrhea cases still have unknown etiology
50
Norwalk identification
1st virus identified from stool samples by electron microscopic examination (1972)
Rotaviruses are members of the_________family
Reovirus= Respiratory Enteric Orphan viruses
Reovirus family envelope/caspids
nonenveloped with inner/outer capsids
rotavirus/reovirus replication
enters via endocytosis
full genome replication
uses own RNA poly
buds from ER
genome of rotaviruses
11 segments of double-stranded RNA (dsRNA)
end result rotavirus infection on cell
Lysis of infected cells
Rotaviruses may cause?
- potentially fatal dehydration
transmission of rotaviruses
what allows them to be transmitted this way?
how infectious?
fecal-oral transmission
acid stability conferred by double capsid structure
up to 10^12 virus particles per ml stool and as few as 10 virus particles can cause infection
how do rotaviruses cause potentially fatal diarrhea
virus produces an enterotoxin
binds integrins; signaling results secretion of chloride and water
infected gut epithelial cells destroyed & replaced by immature epithelial cells (reduced uptake of ions, water; less absorption of foods molecules (carbs))
most common group of rotaviruses in US
group A
rotavirus vax?
Rotavirus vaccine for infants (>75% effective)
norovirus genome/ strucutre
+ RNA
naked capsid virions
norovirus replication, similar to what other virus?
Replication similar to picornaviruses (poliovirus) except 2nd phase of translation involves subgenomic RNAs (like coronaviruses).
Has a 5VPg protein on RNA (like picornaviruses)
Adenovirus
genome
structure/ geometry
linear dsDNA
non enveloped
iscohedral
adenovirus cell entry
•Adenovirus attaches to receptors on surface of host cells (CAR = coxsackievirus
adenovirus receptor)
•most cells express CAR
•receptor-mediated endocytosis
•pH drop in endosome induces viral uncoating
•endosome ruptures, releasing contents into cytoplasm
•viral nucleoprotein complex enter cell nucleus
adenovirus gene expression and transcription regulators
where does viral DNA go?
Adenovirus gene expression temporal regulation: pre-early, early, late genes
RNAs are spliced
transcriptional regulators produced during one phase act to promote transcription of genes of subsequent phase
VIRAL DNA ENTERS NUCLEUS
adenovirus DNA replication, priming?
only one of the 2 DNA strands is copied at each replication fork no discontinuous replication (lagging strand replication)
priming is by a viral protein, pTP (preterminal protein)
strand not copied can self bind and be primed for replication
what primes adenovirus DNA syn
Priming of DNA synthesis by pTP serine residue
adenovirus infections commonality?
symptoms?
widespread: 5-10% of all viral infections
similar to common cold
adenovirus vax type
targets which serotypes?
Vaccine (live virus) given to new military recruits
targets serotypes 4 and 7
acute respiratory disease (ARD) caused by what virus/serotypes
adenovirus serotypes 4, 7, and 21
adenovirus interference with host cell function
interefers with gene expression to reduce mRNA transport/ translation= stops host cell pro synthesis
adenovirus Mechanisms for evasion of host defense
block MHC class I mRNA production
block transport of MHC class I proteins to the cell surface viral E3gp19K protein does this= results in block of killing by cytotoxic T cells
Adenovirus
E3 region
cluster of genes mediating evasion of host defense
adenovirus will drive the host cell into?
why?
proteins used? actions?
can potentially lead to what state?
Adenovirus drives the host cell into cell division
necessary for adenovirus to replicate (needs cellular S phase factors)
Adenovirus E1a and E1b proteins interfere with cell division controllers
E1b sequesters p53 and E1a sequesters Rb (retinoblastoma protein)
Viral infection can potentially drive a cell toward a cancerous state
Brief background on cell cycle factors: Rb and E2F example
Example: DNA damage during G1
P53 recognizes DNA damage and activates P21 (p53 recognizes certain types of DNA mismatches)
P21 binds and inactivates the cyclin-CDK complex which has already begun to be produced in
response to different signals
DNA repaired, p53 decreases, P21 no longer blocks cyclin-CDK, cell cycle progression
P53 act as a checkpoint controller to stop cell-cycle progression
Inactivation of p53 by adenovirus
done by E1b protein- prevents activation of p21 (and Bax)
Adenovirus E1a protein
binding to Rb complex prevents Rb from negatively regulating E2f
Human papillomaviruses
genomes and strucutres
circular dsDNA
non enveloped
Human papilloma viruses (HPV) serotypes
100s
types of HPV
mucosal or cutaneous
HPV infection process timeframe
3-4 month process (usually)
HPV access into body
what stimulates early growth?
HPV accesses basal layer through breaks in skin
Viral early genes stimulate cell growth (which facilitates viral replication)
HPV reproduction coordinated with? HPV gene expression? late proteins made when? Assembly? nuclear remnants shed?
HPV reproduction coordinated with development of keratinocytes (Keratinocytes = nondividing, physical barrier; nuclear)
As cells move through skin layers HPV gene expression and DNA replication begins (uses cellular DNA polymerase)
Late proteins (capsid proteins) only made in differentiated layers
Assembly occurs in nucleus during keratinocyte development
Nuclear remnant with viral particles shed at skin surface. HPVs are not lytic.
Koilocytes
enlarged keratinocytes with clear halos around enlarged nuclei - characteristic of HPV infection
HPV spread by?
skin-to-skin contact: breaks in skin or example, scratching mucous membranes more susceptible
sexual contact
During birth
HPV oral/ airway symptoms
Warts of oropharynx
laryngeal papillomas (HPV-6 and -11)
respiratory papillomatosis: hoarseness is usual symptom (signify obstructing HPV lesions) respiratory distress and secondary bacterial pneumonia in children
most benign tumors of oral cavities
HPV Single oral papillomas are the most benign epithelial tumors of the oral cavity
Anogenital warts, main strains?
condylomata acuminata (90% caused by HPV-6 and -11)
Cervical papillomas
%?
strains?
HPV is present in 99.7% of a cervical cancers
>85% of cervical carcinomas contain integrated HPV DNA
HPV 16 and 18 (and 31& 45) are high-risk types
detection of cervical cancer
Koilocytic cells in Pap smears indicate HPV
HPV infection often visable?
Often infections are not recognizable (asymptomatic)
up to 50% of a population positive for HPV DNA but majority
have no visible evidence of infection
HPV prevention
vax available for strains 16 and 18, prevention of cervical cancer
HPV proteins important in cancer
The HPV E6 and E7 proteins are important for cancer development.
They are the only 2 HPV proteins always expressed in cervical cancer cells.
HPV E6 protein action
Inactivation of p53: leads to ubiquitination of p53 and degradation
E7 protein action
prevents Rb from controlling cell division
these proteins bind Rb complex and prevent Rb from negatively regulating E2f
E2f is now free to activate transcription of cellular DNA synthesis genes.
